title: Celiac Disease-Specific TG2-Targeted Autoantibodies Inhibit Angiogenesis Ex Vivo and In Vivo in Mice by Interfering with Endothelial Cell Dynamics.
abstract: A characteristic feature of celiac disease is the presence of circulating autoantibodies targeted against transglutaminase 2 (TG2), reputed to have a function in angiogenesis. In this study we investigated whether TG2-specific autoantibodies derived from celiac patients inhibit angiogenesis in both ex vivo and in vivo models and sought to clarify the mechanism behind this phenomenon. We used the ex vivo murine aorta-ring and the in vivo mouse matrigel-plug assays to address aforementioned issues. We found angiogenesis to be impaired as a result of celiac disease antibody supplementation in both systems. Our results also showed the dynamics of endothelial cells was affected in the presence of celiac antibodies. In the in vivo angiogenesis assays, the vessels formed were able to transport blood despite impairment of functionality after treatment with celiac autoantibodies, as revealed by positron emission tomography. We conclude that celiac autoantibodies inhibit angiogenesis ex vivo and in vivo and impair vascular functionality. Our data suggest that the anti-angiogenic mechanism of the celiac disease-specific autoantibodies involves extracellular TG2 and inhibited endothelial cell mobility.
authors.affiliation: Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Suvi
authors.initials: S
authors.lastname: Kalliokoski
authors.forename: Ana-Marija
authors.initials: AM
authors.lastname: Sulic
authors.forename: Ilma R
authors.initials: IR
authors.lastname: Korponay-Szabó
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Szondy
authors.forename: Rafael
authors.initials: R
authors.lastname: Frias
authors.forename: Mileidys Alea
authors.initials: MA
authors.lastname: Perez
authors.forename: Stefania
authors.initials: S
authors.lastname: Martucciello
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.forename: Lauri J
authors.initials: LJ
authors.lastname: Pelliniemi
authors.forename: Carla
authors.initials: C
authors.lastname: Esposito
authors.forename: Martin
authors.initials: M
authors.lastname: Griffin
authors.forename: Daniele
authors.initials: D
authors.lastname: Sblattero
authors.forename: Markku
authors.initials: M
authors.lastname: Mäki
authors.forename: Katri
authors.initials: K
authors.lastname: Kaukinen
authors.forename: Katri
authors.initials: K
authors.lastname: Lindfors
authors.forename: Sergio
authors.initials: S
authors.lastname: Caja
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002446:Celiac Disease / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000276:immunology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins